Sophia N. Kouni

Penicillin allergy in cancer patients manifesting as Kounis syndrome.

Two cases of allergic angina and allergic myocardial infarction (Kounis syndrome) following penicillin administration are described. The patients suffered from lung and mandible neoplasms and had previously received several courses of antineoplastic therapy without any sequelae. One patient had normal coronary arteries (type I variant of the syndrome) and the other had coronary artery disease with previous myocardial infarction (type II variant of the syndrome). The allergic reaction following penicillin administration seemed to have triggered the development of an acute coronary artery spasm in the first patient and an acute myocardial infarction in the second. This report shows that susceptible individuals expressing a magnified mast cell degranulation effect may be more vulnerable to coronary artery spasm and plaque erosion or rupture.

Pneumomediastinum and Cervical Emphysema Associated with Unusual Clinical and Electrocardiographic Manifestations A Case Report

This is the first case reported of combined cervical emphysema and pneumomediastinum asso ciated with unusual electrocardiographic and local neurologic findings. These may be the result of an increase in intracervical and intrathoracic pressure induced by the dissecting air.

Ascites and other extracardiac manifestations associated with right atrial myxoma : A case report

Right atrial myxomas are rare intracardiac tumors that often pose difficulties in diagnosis. Right ventricular failure and ascites ensuing from tricuspid valve orifice obstruction are potentially dangerous complications. Early diagnosis of cardiac myxoma is important since surgical treatment leads to disappearance of all symptoms with a low rate of recurrence and good long-term survival. Nonspecific extracardiac symptoms, signs, complications, and laboratory findings may be the initial manifestations contributing to misdiagnosis of these rare but totally treatable atrial tumors.

Allergy to Heparins, Thrombosis, Thrombocytopaenia and Kounis Syndrome: A Clinical Paradox

When antigenic complexes bridge nearby antibodies on the mast cell surface and the critical number of bridged IgE antibodies reaches the order of 2000 out of maximal number of some 500 000–1 000 000 in order to make 1000 bridges, then mast cell degranulation ensues and a variety of inflammatory mediators are released locally and in the systemic circulation [1]. Such mediators can induce either coronary artery spasm which can progress to acute myocardial infarction or atheromatous plaque erosion or rupture culminating in coronary thrombosis [2]. The released mediators include biogenic amines such as histamine, enzymes such as neutral proteases including chymase, tryptase and cathepsin-D, chemokines, cytokines, peptides, proteoglycans, growth factors and arachidonic acid products such as leukotrienes, prostacyclin, tumour necrosis factor-a, platelet activating factor (PAF) and thromboxane. Plaque erosion or rupture-associated coronary thrombosis and thrombosis in general are the result of serial platelet adhesion, activation and aggregation. Platelets bring in their surface, apart from the well-known receptors for thromboxane, adenosine diphosphate and glycoprotein IIb/IIIa, receptors for multiple exogenous agonists which contribute to platelet activation. These include receptors for thrombin, serotonin, epinephrine, PAF, histamine, as well as FcgRI, FcgRII, FceRI and FceRII receptors [3,4]. When the existing platelet receptors for histamine, PAF, thromboxane and FcgRI, FcgRII, FceRI, FceRII are activated by corresponding mediators released during mast cell degranulation the result is the Kounis hypersensitivity associated coronary

Eosinophilic coronary arteritis, hypersensitivity myocarditis and the Kounis hypersensitivity associated acute coronary syndrome

In the very important paper published recently inthis Journal (Omalu, Hammers, DiAngelo, & Luckasevic,2011) the authors described two patients who died sud-denly due to isolated eosinophilic coronary arteritis. Thefirst patient had a past history of hypertension, multiplesclerosis, depression, and thyroid dysfunction attributedto Hashimoto’s thyroiditis. During the following post-mortem examination the anterior descending coronaryartery was found without any thrombus formation butthe adventitia and media were infiltrated by numerouseosinophils. The second patient had also a past historyof hypertension and depression. Microscopic postmortemexamination revealed an acute dissection of the proximalleft anterior descending coronary artery with eosinophilicinfiltration of media and adventitia. The authors of thisreport postulated that sudden death was due to cardiacarrhythmia induced by atraumatic coronary artery dis-section or due to inflammatory coronary vasospasm.However, they did not search for mast cells in thepost-mortem biopsy and they did not refer to the Kounishypersensitivity acute coronary syndrome (Kounis,Mazarakis, Tsigkas, Giannopoulos, & Goudevenos, 2011).Kounis syndrome combines acute coronary syndromeswith conditions associated with mast cell activation, in-volving interrelated and interacting inflammatory cells,and includes anaphylactic or anaphylactoid and allergicor hypersensitivity insults. It is caused by preformed andnewly synthesized inflammatory mediators released dur-ing the anaphylactic process. A subset of platelets bearingFC

Kounis hypersensitivity coronary syndrome is associated with presence of older thrombus in patients with late and very late drug-eluting stent thrombosis

Nishihira et al. [1] found that in most patients with late and very ate drug-eluting stent thrombosis, the creation of thrombus is not n acute event but starts at least days to weeks before culminatng in an acute event. The authors concluded that their findings rovide further information about another potential mechanism f drug-eluting stent thrombosis. However, they have not referred o hypersensitivity coronary syndrome and they have not stained he aspirated thrombus for eosinophilic infiltration. We strongly elieve that stent thrombosis and late stent thrombosis are, mainly, anifestations of the Kounis hypersensitivity associated coronary yndrome [2] caused by an “antigenic complex” of nickel alloys, olymers, eluted drugs, and possibly concominant oral antiplatelet rugs and environmental exposures. So far, all animal studies and xperiments, reported pathology findings, and clinical reports in ll patients who have died from stent thrombosis, point toward hypersensitivity inflammation with infiltration of various interelated and interacting inflammatory cells including eosinophils, acrophages, T-cells, and mast cells. Eosinophils are bone marrowerived granulocytic leukocytes, which normally reside in tissues nd express H4 histamine receptors. These receptors facilitate osinophil chemotaxis toward mast cells, which are the major proucers of histamine. Both eosinophils and mast cells are important ffector cells in the late phase allergic response and they have been mplicated in the pathogenesis of allergic diseases. Eosinophils espond to histamine by changing cell shape, upregulation of adheion molecules, and chemotaxis, and these responses are mediated y the H4 receptor expressed on eosinophils. Hypersensitivity inflammation goes through three phases [3], he early phase which lasts minutes, the late phase which lasts from h to 2 days, and the chronic phase which follows a continuous, ersistent, and repetitive allergen exposure and lasts as long as the llergen is present. It seems likely that early, late, and very late stent hrombosis correspond temporally with the early, late, and chronic llergic inflammation independently of level of documentation as efinite or confirmed, probable and possible. Indeed, the findings f Nishihira et al. [1] are compatible and may temporally correpond with the early, late, and chronic phases of hypersensitivity nflammatory process. The newer stents bearing the misleading erm cobalt–chromium or platinum–chromium stents and eluting he sirolimus analogues everolimus and zotarolimus both contain ickel and other metals. Nickel hypersensitivity is a ubiquitous pheomenon and may reach the level of 24.6% [4]. Human platelets re activated through receptors for multiple agonists but a subet of platelets contains FC RI and FC RII IgE receptors [5] which ould be activated by corresponding antigens. Everolimus stents ontain about 10% nickel and zotarolimus stents contain 35% nickel nd despite the stent electropolishing and polymer coverage still elease nickel ions locally and in systemic circulation.

A novel method of brainstem auditory evoked potentials using complex verbal stimuli

Background: The click and tone-evoked auditory brainstem responses are widely used in clinical practice due to their consistency and predictability. More recently, the speech-evoked responses have been used to evaluate subcortical processing of complex signals, not revealed by responses to clicks and tones. Aims: Disyllable stimuli corresponding to familiar words can induce a pattern of voltage fluctuations in the brain stem resulting in a familiar waveform, and they can yield better information about brain stem nuclei along the ascending central auditory pathway. Materials and Methods: We describe a new method with the use of the disyllable word “baba” corresponding to English “daddy” that is commonly used in many other ethnic languages spanning from West Africa to the Eastern Mediterranean all the way to the East Asia. Results: This method was applied in 20 young adults institutionally diagnosed as dyslexic (10 subjects) or light dyslexic (10 subjects) who were matched with 20 sex, age, education, hearing sensitivity, and IQ-matched normal subjects. The absolute peak latencies of the negative wave C and the interpeak latencies of A-C elicited by verbal stimuli “baba” were found to be significantly increased in the dyslexic group in comparison with the control group. Conclusions: The method is easy and helpful to diagnose abnormalities affecting the auditory pathway, to identify subjects with early perception and cortical representation abnormalities, and to apply the suitable therapeutic and rehabilitation management.